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A poor-quality human liver, rejected by all transplant centers, was treated outside the body for 3 days using a perfusion machine that simulated some functions of the human body and has been successfully transplanted into a patient with advanced cirrhosis.

The 62-year-old patient rapidly returned to normal quality of life and at the 1-year follow-up had no signs of liver damage, such as rejection or bile duct injury, according to the report published in Nature Biotechnology.

The study team was led by Pierre-Alain Clavien, MD, PhD, pharmacy in mexico with the department of surgery and transplantation, Swiss Hepato-Pancreato-Biliary and Transplant Center, University Hospital Zürich, and the Wyss Zürich Translational Center, ETH Zürich and University of Zürich.

Expanding the Viability Window

Livers for transplant are routinely preserved in a static cold solution and implanted within a few hours. Most centers limit the time in the cold solution to 12 hours as the organ’s viability drops quickly after that time.

“This inaugural clinical success opens new horizons in clinical research and promises an extended time window of up to 10 days for assessment of viability of donor organs as well as converting an urgent and highly demanding surgery into an elective procedure,” the authors wrote.

The Liver4Life team, made up of physicians, engineers, and biochemists, developed the complex perfusion machine. Features of the machine, which mimics human body functions, include automated remote control of all key parameters. A pump mimics the heart, an oxygenator replaces the lungs, and a dialysis unit performs as kidneys would. Hormone and nutrient infusions take over the work of the intestines and pancreas. The machine also moves the liver to the rhythm of simulated breathing.

The team had to solve factors that limit viability for any solid organ outside the body over a few hours including hemolysis, hemodynamic stability, glucose control, pathologic glycogen deposition and perfusate quality and dilution.

Additionally, because the organ would be under machine perfusion for several days, the scientists also had to address pressure necrosis.

History Behind the Procedure

The process started in 2015 with the support of the Wyss Zürich Translational Center, with the goal of long-term ex situ machine perfusion of injured liver grafts.

As part of the agreement from the Swiss regulatory authority (the Federal Office of Public Health) the process would be used only if the organ was rejected by all transplant centers, the recipient had no other options for a donor liver, and if the organ met a rigorous bar for viability.

On May 19, 2021, the team was offered a liver graft from a 29-year-old female donor who had an invasive abdominal desmoid fibromatosis associated with chronic intra-abdominal abscesses and recurrent sepsis episodes from multiresistant bacteria. The donor needed long-term multiple medications and parenteral nutrition. Additionally, there was a 4-cm tumor in segment 1 of the liver.

The liver was refused by all other centers, “primarily because it required diagnostic workup of the liver lesion, which was not immediately possible, and because of the ongoing sepsis in the donor with multiresistant microorganisms,” the authors wrote.

The team removed the liver, and the graft was connected to the Wyss perfusion device for normothermic (37 °C) ex situ perfusion after 4 hours of cold preservation.

A 62-year-old male potential recipient on the official national transplant list, had earlier agreed to be considered for receiving a graft preserved ex situ in the Wyss machine.

The patient was fully informed about the process and the presence of a benign lesion in the graft and accepted the transplantation procedure. The patient had advanced cirrhosis, severe portal hypertension, and multiple and recurrent hepatocellular carcinoma (HCC).

Recipient Had ‘Near-Zero’ Chance to Get a Liver in Time

The authors wrote that the patient had “a near-zero chance to receive a graft in time.”

For patients with HCC in Switzerland, the wait for liver transplant is longer than a year and no living-donor options were available.

The transplant operation took 5 hours and 26 minutes, and blood loss was limited (600 mL). No transfusion was required. The patient was extubated in the operating room, transferred to the ICU, and discharged 12 days later.

Because a biopsy showed no detectable liver injury or rejection, and based on previous evidence of lower immunogenicity in perfused livers and kidneys, the researchers chose a reduced immunosuppressive regimen with quickly tapering steroids. The steroids were completely discontinued 6 weeks after surgery.

The authors wrote: “In our experience, the absence or very low degree of reperfusion injury seen in our transplant is observed only in living donation, where ‘close-to-perfect’ livers from healthy young donors are transplanted immediately as both donors and recipient are operated in parallel.”

In a press release, the team said the next step is to assess the procedure in other patients in a multicenter study.

Clavien and several coauthors affiliated with ETH (the Swiss Federal Institute of Technology in Zürich) and the University of Zürich have applied for patents on this new perfusion technology. No other authors have any competing interests.

This article originally appeared on MDedge.com, part of the Medscape Professional Network.

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